Abstract: This invention provides an oral pharmaceutical composition comprising a physiologically tolerable gelled oil-in-water emulsion containing a drug of abuse.
Type:
Application
Filed:
April 11, 2011
Publication date:
October 17, 2013
Applicant:
AYANDA GROUP AS
Inventors:
Kurt Ingar Draget, Ingvild Johanne Haug, Steinar Johan Engelsen, Tore Seternes, Magnus N. Hattrem
Abstract: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.
Type:
Application
Filed:
May 7, 2013
Publication date:
October 3, 2013
Applicant:
KemPharm, Inc.
Inventors:
Travis Mickle, Sven Guenther, Christal Mickle, Guochen Chi, Jaroslaw Kanski, Andrea K. Martin, Bindu Bera
Abstract: The present invention relates to an improved process for preparing morphinane analogues of formula (1) wherein the substituents R1, R2, R3, R4, R5 and Y have the same meanings as defined in the specification.
Abstract: The present invention provides a compound of formula I: wherein R1, R2, R2? and X? are as defined and described herein, methods of manufacture thereof and compositions thereof, useful for example as peripheral mu opioid receptor antagonists in treatment of side effects of opioid administration.
Abstract: The present invention relates to the Nalmefene hydrochloride dihydrate, methods of manufacturing Nalmefene hydrochloride dihydrate, a pharmaceutical composition comprising Nalmefene hydrochloride dihydrate and a method of treatment comprising administering Nalmefene hydrochloride dihydrate.
Type:
Grant
Filed:
December 4, 2009
Date of Patent:
September 10, 2013
Assignees:
H. Lundbeck A/S, Bioei Therapies Corp
Inventors:
Heidi Lopez de Diego, Carla de Faveri, Florian Anton Martin Huber
Abstract: Stable crystalline forms of a compound represented by the formula (IA): an acid addition salt, and/or a solvate thereof are provided by the present invention. Said crystalline forms are extremely useful as materials for preparing medicines. Novel processes for preparing 6,7-unsaturated-7-carbamoyl morphinan derivatives are also provided by the present invention.
Abstract: The present invention is directed to the preparation of 6-hydroxy morphinans having formula (II) or N-alkylated 6-hydroxy morphinans having formula (III).
Type:
Grant
Filed:
December 3, 2009
Date of Patent:
September 3, 2013
Assignee:
Mallinckrodt LLC
Inventors:
Christopher W. Grote, Peter X. Wang, Tao Jiang, Gary L. Cantrell, Frank W. Moser, Catherine E. Thomasson
Abstract: The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.
Type:
Grant
Filed:
June 10, 2010
Date of Patent:
August 27, 2013
Assignee:
Mallinckrodt LLC
Inventors:
Christopher W. Grote, Gary L. Cantrell, Joseph P. McClurg, Catherine E. Thomasson, Frank W. Moser
Abstract: The present invention provides processes for preparing nal-opiates without the isolation of intermediates. In general, the process provides for alkylation and reduction in the same pot to give the nal-opiate.
Abstract: The present invention is directed to an improved poppy straw, concentrate of poppy straw and opium of Papaver somniferum for the production of codeine containing little or no oripavine, morphine or thebaine. The present invention also provides plants, stands and seeds of Papaver somniferum and methods for the production of codeine.
Abstract: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydromorphone (4,5-?-epoxy-3-hydroxy-17-methyl morphinan-6-one) to form novel prodrugs/compositions of hydromorphone. The hydromorphone prodrugs of the present technology have decreased side effects and decreased potential for abuse compared to unconjugated hydromorphone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.
Abstract: The disclosure relates to derivatives of morphine-6-glucuronide of formula (I) wherein R1 is as defined in the disclosure, or an acid addition salt thereof, as well as in hydrate or solvate form. The disclosure also relates to the preparation method thereof and to the use of same in therapeutics.
Abstract: The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligomer.
Type:
Grant
Filed:
March 21, 2012
Date of Patent:
May 14, 2013
Assignee:
Nektar Therapeutics
Inventors:
Jennifer Riggs-Sauthier, Bo-Liang Deng, Timothy A. Riley
Abstract: The present invention relates to ester prodrugs of nalmefene of formula (I), pharmaceutical compositions comprising these compounds, chemical processes for preparing these compounds and their use in the treatment of substance abuse disorders such as alcohol abuse and alcohol dependence and impulse control disorders such as pathological gambling and addiction to shopping.
Type:
Grant
Filed:
April 23, 2009
Date of Patent:
May 14, 2013
Assignee:
Janssen Pharmaceutica NV
Inventors:
Michel Joseph Maurice André Guillaume, Tim Gaekens
Abstract: The disclosure relates to compounds of formula (I): wherein R1, R2, and n are as defined in the disclosure, and addition salts solvates and hydrates thereof. The disclosure also relates to the preparation method of said compounds and to the use of the same in therapeutics.
Abstract: The invention provides a process for the N-alkylation of normorphinan compounds to produce N-alkylated morphinan compounds. In particular, the process relates to the alkylation of a normorphinan compound by a carboxaldehyde in the presence of a reducing agent to form an N-alkylated morphinan.
Abstract: The present disclosure generally relates to methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydromorphone, hydrocodone, or a derivative thereof, by means of a non-catalytic hydrogenation reaction of thebaine, oripavine or a derivative thereof, respectively, using a hydrazide reagent, followed by hydrolysis of the hydrogenated intermediate at a low temperature and for a short period of time. Additionally, the present disclosure relates to a composition comprising the desired hydromorphone, hydrocodone, or a derivative thereof, in combination with a 6-beta compound that is structurally related thereto.
Abstract: This invention relates to the discovery of novel polymorphic forms of naltrexone, including solvates, hydrates, anhydrous and other crystalline forms and combinations thereof. These novel forms of naltrexone impart advantages in pharmaceutical formulations incorporating them, including sustained release, or long acting, formulations.
Type:
Grant
Filed:
September 25, 2007
Date of Patent:
March 5, 2013
Assignee:
Alkermes, Inc.
Inventors:
Harry G. Brittain, David A. Dickason, Joyce M. Hotz, Shawn L. Lyons, J. Michael Ramstack, Steven G. Wright
Abstract: The present disclosure generally relates to catalytic methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydrocodone, hydromorphone, or a derivative thereof, by means of a conversion or an isomerization of codeine, morphine, or a derivative thereof, respectively, using a heterogeneous ruthenium metal catalyst.
Abstract: 4-Fluoro-4-phenylpiperidin-1-yl ? antagonists of general structure as well as pharmaceutical compositions comprising compounds of formula I, are disclosed. These compounds and compositions are useful as treatments of conditions or diseases associated with binding opioid receptors including pain, obesity, hyperalgesia, inflammation, osteoarthritis, drug addiction, and cancer. These compounds and compositions are also useful as treatments for tardive dyskinesia.
Abstract: The method of altering the alkaloid composition of a poppy plant comprising the step of applying an effective amount of acylcyclohexanedione compound or agriculturally acceptable salt thereof to said poppy plant or locus thereof. Further, the present invention also provides the method of altering the alkaloid composition of a poppy plant comprising the step of applying an effective amount of methyl jasmonate or agriculturally acceptable salt thereof to said poppy plant or locus thereof.
Abstract: A drug substance with a pharmaceutically acceptable organic acid addition salt of an opioid wherein said organic acid is selected from Structure A: wherein R1-R4 are independently selected from H, alkyl or substituted alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl, or cyclic aryl moiety; R5 is selected from H, or an alkali earth cation; R6 and R7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and wherein X is selected from nitrogen, oxygen or sulfur; and wherein the drug substance has a morphology selected from amorphous and crystalline.
Type:
Grant
Filed:
December 29, 2011
Date of Patent:
February 5, 2013
Assignee:
Pisgah Laboratories, Inc.
Inventors:
Clifford Riley King, Stephen G. D'Ambrosio, David W. Bristol, Michael L. English
Abstract: Provided are methods for reducing the addiction potential and/or reducing one or more CNS-side effects related to the administration of an opioid analgesic drug by administering the opioid analgesic drug in the form of an oligomeric polyethylene glycol conjugate compound. The compounds provided demonstrate notably reduced potential for substance abuse, and possess altered pharmacokinetic profiles relative to the opioid agonists alone, but are not subject to the risk of physical tampering that allows for the recovery and abuse of the opioid agonist associated with certain alternative delivery formulations.
Type:
Application
Filed:
January 12, 2011
Publication date:
January 24, 2013
Applicant:
Nektar Therapeutics
Inventors:
C. Simone Jude-Fishburn, Timothy A. Riley, Alberto N. Zacarias, Hema Gursahani
Abstract: Methods are provided which include converting oripavine to other opiates, including converting oripavine to naltrexone, buprenorphine, 14-hydroxymorphinone and/or converting 14-hydroxymorphinone to oxymorphone. Purification and salt formation are optionally included.
Abstract: A synthetic method is provided, wherein the method comprises stereoselectively reducing a ketone of a morphinone to form a reduced morphinone and optionally covalently attaching a water soluble polymer to the reduced morphinone.
Abstract: The present invention relates to compounds of Formula I or II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which relates to morphinan compounds useful as ?, ?, and/or ? receptor opioid compounds and pharmaceuticals containing same that may be useful for mediating analgesia, combating drug addiction, alcohol addiction, drug overdose, mental illness, bladder dysfunctions, neurogenic bladder, interstitial cystitis, urinary incontinence, premature ejaculation, inflammatory pain, peripherally mediated and neuropathic pain, cough, lung edema, diarrhea, cardiac disorders, cardioprotection, depression, and cognitive, respiratory, diarrhea, irritable bowel syndrome and gastro-intestinal disorders, immunomodulation, and anti-tumor agents.
Type:
Grant
Filed:
February 13, 2009
Date of Patent:
January 15, 2013
Assignee:
Alkermes, Inc.
Inventors:
Derrick Arnelle, Daniel Deaver, Reginald L. Dean, III, Mark Todtenkopf
Abstract: A drug substance with a pharmaceutically acceptable organic acid addition salt of an opioid wherein said organic acid is selected from Structure A: wherein R1-R4 are independently selected from H, alkyl or substituted alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl, or cyclic aryl moiety; R5 is selected from H, or an alkali earth cation; R6 and R7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and wherein X is selected from nitrogen, oxygen or sulfur; and wherein the drug substance has a morphology selected from amorphous and crystalline.
Type:
Grant
Filed:
December 28, 2011
Date of Patent:
December 25, 2012
Assignee:
Pisgah Laboratories, Inc.
Inventors:
Clifford Riley King, Stephen G. D'Ambrosio, David W. Bristol, Michael L. English
Abstract: A drug substance with a pharmaceutically acceptable organic acid addition salt of an opioid wherein said organic acid is selected from Structure A: wherein R1-R4 are independently selected from H, alkyl or substituted alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl, or cyclic aryl moiety; R5 is selected from H, or an alkali earth cation; R6 and R7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and wherein X is selected from nitrogen, oxygen or sulfur; and wherein the drug substance has a morphology selected from amorphous and crystalline.
Type:
Grant
Filed:
January 18, 2011
Date of Patent:
December 11, 2012
Assignee:
Pisgah Laboratories, Inc.
Inventors:
Clifford Riley King, Stephen G. D'Ambrosio, David W. Bristol, Michael L. English
Abstract: Process for the preparation of N-methylnaltrexone bromide, wherein a compound of the general formula (I): wherein X? represents an anion other than the bromide anion, and R represents hydrogen or a leaving group, is dissolved or dispersed in a suitable polar solvent, the solution or dispersion is mixed with a compound containing bromide anions, and the resulting reaction mixture is stirred until N-methylnaltrexone bromide has formed and crystallized, wherein, in the case where R represents a leaving group, that group is removed during or after the reaction.
Type:
Grant
Filed:
May 14, 2008
Date of Patent:
November 27, 2012
Assignee:
Cilag AG
Inventors:
Ulrich Weigl, Pascal Schär, Alfred Stutz
Abstract: The present invention provides processes for the preparation of 10-keto and/or 10-hydroxy morphinans. In particular, the invention provides to processes for preparing a 10-keto morphinan by chromium-catalyzed benzylic oxidation of a morphinan with a periodic acid.
Type:
Grant
Filed:
September 7, 2010
Date of Patent:
November 20, 2012
Assignee:
Mallinckrodt LLC
Inventors:
Hang Sun, John E. Johnson, Jr., Ricky L. Fenton, Sarah M. Dorn
Abstract: An improved opiate synthesis scheme is provided. An improvement to the oxidation of oripavine and oripavine derivatives comprises the in-situ formation of the peroxacids required to oxidize the oripavine and oripavine derivatives to form an intermediate. An improvement to the reduction of the intermediate to form oxycodone and oxycodone derivatives comprises reduction utilizing a hydrogen transfer reagent. These improvements allow the production of oxycodone and oxycodone derivatives without isolation of the intermediate, providing a one-pot synthesis method.
Type:
Grant
Filed:
April 15, 2008
Date of Patent:
November 13, 2012
Assignee:
Mallinckrodt LLC
Inventors:
Peter X. Wang, Tao Jiang, Gary L. Cantrell, David Wayne Berberich
Abstract: The present application is directed to an efficient conversion of C-14 hydroxylated morphine alkaloids to various morphine analogs, such as naltrexone, naloxone and nalbuphone. One feature of this process is an intramolecular functional group transfer from the C-14 hydroxyl to the N-17 nitrogen atom following a palladium-catalyzed N-demethylation.
Abstract: Indole alkaloid derivatives having an opioid receptor agonistic effect, their synthesis, and therapeutic compositions containing these derivatives, and methods of treating conditions with these compounds and therapeutic compositions, are provided.
Type:
Application
Filed:
July 16, 2012
Publication date:
November 1, 2012
Applicants:
JOSAI UNIVERSITY CORPORATION, NATIONAL UNIVERSITY CORPORATION CHIBA UNIVERSITY
Abstract: The present invention provides processes for the synthesis of opiate alkaloids. In particular, the opiate alkaloids produced by the process of the invention are typically intermediate compounds that may be utilized to produce a variety of biologically active alkaloids including buprenorphine and diprenorphine.
Abstract: The present invention is generally directed to a process for the preparation of a ketomorphinan comprising maintaining a ketone group as unprotected and performing reductive amination using a hydrogen source and a catalyst.
Type:
Grant
Filed:
September 29, 2009
Date of Patent:
September 18, 2012
Assignee:
Mallinckrodt LLC
Inventors:
Edmund C. Hudson, Douglas Teramura, Christopher W. Grote, Catherine E. Thomasson, Gary L. Cantrell
Abstract: A method of providing a patient with controlled release of ketone-containing opioid using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing the ketone-containing opioid is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of the ketone-containing opioid from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.
Type:
Application
Filed:
April 21, 2010
Publication date:
September 13, 2012
Inventors:
Thomas E. Jenkins, Craig O. Husfeld, Julie D. Seroogy, Jonathan W. Wray
Abstract: The present invention provides methods of N-demethylating, N-methylated heterocycles and N-methyl, N-oxide heterocycles using a transition metal with an oxidation state of zero, ferrocene or substituted derivatives thereof, or Cr3+. N-demethylated heterocycles prepared by the methods of the present invention are also provided.
Abstract: The disclosure relates to a method for preparing morphine-6-glucuronide or one of the deritives thereof comprising reacting a compound of formula (I): wherein R1 is as defined in the disclosure, with a glucuronic acid derivative of formula (II): wherein PG, X, and R4 are as defined in the disclosure, in the presence of an aromatic solvent and trimethylsilyl trifluoromethanesulfonate; (ii) reacting the product obtained in step (i) with a strong basic agent; and then (iii) recovering the product obtained in step (ii).
Abstract: The present invention provides processes for the synthesis of five and six membered rings. In particular, the present invention provides processes for the synthesis of five and six membered rings in alkaloids.
Type:
Grant
Filed:
September 14, 2009
Date of Patent:
August 28, 2012
Assignee:
Mallinckrodt LLC.
Inventors:
Peter X. Wang, Tao Jiang, David W. Berberich
Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2—OH, —CH2NH2, —NHSO2CH3, and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.
Abstract: The present invention relates to a process for the reduction of a 6-keto group in a morphinan alkaloid to the corresponding 6-hydroxy group, comprising hydrogenating the 6-keto group using gaseous hydrogen in the presence of a heterogenous catalyst and a solvent, to yield the 6-hydroxy morphinan alkaloid, wherein the reduction is carried out at a pH in the range of about 5 to about 7, and the 6-hydroxy morphinan alkaloid has an ?:? ratio of >85:15.
Type:
Application
Filed:
August 13, 2010
Publication date:
August 16, 2012
Applicant:
JOHNSON MATTHEY PUBLIC LIMITED COMPANY
Inventors:
George Scott Wilson, Maureen Joan Young
Abstract: The present invention provides a process whereby morphinan-6-ones can be converted stereospecifically to the corresponding morphinan-6?-ols by catalytic hydrogenation under basic conditions.
Abstract: The present invention provides process for the production of opiate alkaloids. In particular, the present invention provides processes for the production of buprenorphine or a derivative of buprenorphine that minimizes the formation of impurities.
Type:
Grant
Filed:
September 29, 2009
Date of Patent:
July 31, 2012
Assignee:
Mallinckrodt LLC
Inventors:
Brenda E. Allen, Esa T. Jarvi, Dennis J. Kalota, James R. Meyer, Keith G. Tomazi, Anthony Mannino, Brian Orr
Abstract: The invention provides processes for the production of opiate alkaloids. In particular, the present invention provides processes for the formation of opiate alkaloids that minimizes the formation of impurities.
Abstract: The present invention provides polymorphs of 6-beta-naltrexol and process for their preparation. In particular, the present invention provides crystalline forms of the free base of 6-beta-naltrexol and processes for their preparation. The present invention also provides crystalline and amorphous forms of the hydrochloride salt of 6-beta-naltrexol and processes for their preparation.
Abstract: The present invention encompasses compositions comprising UGT inhibitors. Additionally, the invention encompasses methods of reducing the glucuronidation of a compound using a UGT inhibitor.
Type:
Application
Filed:
February 27, 2012
Publication date:
July 19, 2012
Applicant:
The Board of Trustees of the University of Arkansas
Abstract: A method of converting a treatment for pain comprising intravenous administration of opioids, to a treatment for pain comprising oral administration of a first dose of an immediate release morphine-oxycodone combination in patients in need of analgesia. The method may comprise (1) determining a four-hour average oral morphine equivalents, a one-hour average oral morphine equivalents, or determining a net average hourly intravenous dose, and (2) orally administering to the patient a first dose of a morphine-oxycodone combination in a 3:2 ratio by weight every four to six hours. Also, a method of treating pain in patients who had been administered opioids intravenously, comprising using a dosing algorithm to determine the first dose of the immediate release morphine-oxycodone combination.
Type:
Grant
Filed:
July 18, 2011
Date of Patent:
July 17, 2012
Assignee:
QRxPharma Ltd.
Inventors:
Patricia T. Richards, Warren C. Stern, Laurel J. Mengle-Gaw, Benjamin Schwartz